ENZYMATIC INACTIVATION OF HUMAN ALPHA-1-PROTEINASE INHIBITOR BY NEUTROPHIL MYELOPEROXIDASE

Human myeloperoxidase, in the presence of H2O2 and halide ion, can catalytically inactivate human alpha-1-proteinase inhibitor (α-1-PI), the major plasma inhibitor of elastolytic activity. The rate of inactivation is directly proportional to both the myeloperoxidase and α-1-PI concentrations and inversely proportional to the H2O2 concentration. Amino acid analysis of the oxidized α-1-PI reveals that the only modified amino acid is methionine, which is converted to the sulfoxide form during the course of the reaction. Significantly, this system has no effect on either α-2-macroglobulin (α2M) or α-1-antichymotrypsin (α-1-Achy), two other important plasma proteinase inhibitors, nor can the system be replaced with horseradish peroxidase. Since it has been shown recently that methionine occupies part of the reactive site of α-1-PI, it is possible that the release of myeloperoxidase by leukocytes during phagocytosis inactivates this inhibitor through oxidation of this particular residue, thereby indirectly augmenting the proteolytic activity released by these same cells. © 1979.